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Made available in DSpace on 2022-05-01T15:46:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The aim of this study was to identify novel lncRNA differentially expressed (DE) between divergent animals for beef tenderness and marbling traits in Nellore cattle. Longissimus thoracis muscle samples from the 20 most extreme bulls (of 80 bulls set) for tenderness, tender (n = 10) and tough (n = 10) groups, and marbling trait, high (n = 10) and low (n = 10) groups were used to perform transcriptomic analysis using RNA-Sequencing. For tenderness, 29 lncRNA were DE (p-value ≤ 0.01) in tough beef animals in relation to tender beef animals. We observed that genic lncRNAs, for example, lncRNA_595.1, were overlapping exonic part of the PICK gene, while lncRNA_3097.2 and lncRNA_3129.5 overlapped intronic part of the genes GADL1 and PSMD6. The lncRNA associated with PICK1, GADL1, and PMD6 genes were enriched in the pathways associated with the ionotropic glutamate receptor, gamma-aminobutyric acid synthesis, and the ubiquitin–proteasome pathway. For marbling, 50 lncRNA were DE (p-value ≤ 0.01) in high marbling group compared with low marbling animals. The genic lncRNAs, such as lncRNA_3191.1, were overlapped exonic part of the ITGAL gene, and the lncRNA_512.1, lncRNA_3721.1, and lncRNA_41.4 overlapped intronic parts of the KRAS and MASP1 genes. The KRAS and ITGAL genes were enriched in pathways associated with integrin signaling, which is involved in intracellular signals in response to the extracellular matrix, including cell form, mobility, and mediates progression through the cell cycle. In addition, the lincRNAs identified to marbling trait were associated with several genes related to calcium binding, muscle hypertrophy, skeletal muscle, lipase, and oxidative stress response pathways that seem to play a role important in the physiological processes related to meat quality. These findings bring new insights to better understand the biology mechanisms involved in the gene regulation of these traits, which will be valuable for a further investigation of the interactions between lncRNA and mRNAs, and of how these interactions may affect meat quality traits. School of Agricultural and Veterinarian Sciences São Paulo State University (Unesp), SP Department of Animal Biosciences Centre for Genetic Improvement of Livestock University of Guelph National Council for Scientific and Technological Development (CNPq), SP College of Veterinary and Animal Science São Paulo State University (Unesp), SP School of Agricultural and Veterinarian Sciences São Paulo State University (Unesp), SP College of Veterinary and Animal Science São Paulo State University (Unesp), SP

The molecular mechanisms underlying heat stress tolerance in animals to high temperatures remain unclear. This experiment was performed with Sprague-Dawley rats housed at 22 ℃ (control group; CT), and 42 ℃ for 30 min (H30), 60 min (H60), and 120 min (H120). Transcriptomic analysis using RNA-Sequencing (RNA-Seq) from blood (CT and H120), liver (CT, H30, H60, and H120), and adrenal glands (CT, H30, H60, and H120) was performed. The differentially expressed mRNA isoforms (DEIs) were identified and annotated by the CLC Genomics Workbench. Biological process and metabolic pathway analyses were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. A total of 225, 5,764, and 4,988 DEIs in the blood, liver, and adrenal glands were observed. Furthermore, the number of novel differentially expressed transcript lengths with annotated genes and the novel differentially expressed transcript with non-annotated genes were 136 and 8 in blood, 3,549 and 120 in the liver, as well as 3,078 and 220 in adrenal glands, respectively. A total of 35 genes were involved in the heat stress response, out of which Dnaja1, LOC680121, Chordc1, AABR07011951.1, Hsp90aa1, Hspa1b, Cdkn1a, Hmox1, Bag3 and Dnaja4 were commonly identified in the liver and adrenal glands, suggesting that these genes may regulate heat stress response through interactions between liver and adrenal glands. The results suggest that the identified mRNA isoforms could be considered as potential candidates for selecting mammals to improve thermotolerance.

The molecular mechanisms underlying heat stress tolerance in animals to high temperatures remain unclear. This study identified the differentially expressed mRNA isoforms which narrowed down the most reliable DEG markers and molecular pathways that underlie the mechanisms of thermoregulation. This experiment was performed on Sprague Dawley rats housed at 22 °C (control group; CT), and three acute heat-stressed groups housed at 42 °C for 30 min (H30), 60 min (H60), and 120 min (H120). Earlier, we demonstrated that acute heat stress increased the rectal temperature of rats, caused abnormal changes in the blood biochemical parameters, as well as induced dramatic changes in the expression levels of genes through epigenetics and post-transcriptional regulation. Transcriptomic analysis using RNA-Sequencing (RNA-Seq) data obtained previously from blood (CT and H120), liver (CT, H30, H60, and H120), and adrenal glands (CT, H30, H60, and H120) was performed. The differentially expressed mRNA isoforms (DEIs) were identified and annotated by the CLC Genomics Workbench. Biological process and metabolic pathway analyses were performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. A total of 225, 5764, and 4988 DEIs in the blood, liver, and adrenal glands were observed. Furthermore, the number of novel differentially expressed transcript lengths with annotated genes and novel differentially expressed transcript with non-annotated genes were 136 and 8 in blood, 3549 and 120 in the liver, as well as 3078 and 220 in adrenal glands, respectively. About 35 genes were involved in the heat stress response, out of which, Dnaja1, LOC680121, Chordc1, AABR07011951.1, Hsp90aa1, Hspa1b, Cdkn1a, Hmox1, Bag3, and Dnaja4 were commonly identified in the liver and adrenal glands, suggesting that these genes may regulate heat stress response through interactions between the liver and adrenal glands. In conclusion, this study would enhance our understanding of the complex underlying mechanisms of acute heat stress, and the identified mRNA isoforms and genes can be used as potential candidates for thermotolerance selection in mammals.

Although the genetic correlations between complex traits have been estimated for more than a century, only recently we have started to map and understand the precise localization of the genomic region(s) that underpin these correlations. Reproductive traits are often genetically correlated. Yet, we don’t fully understand the complexities, synergism, or trade-offs between male and female fertility. In this study, we used reproductive traits in two cattle populations (Brahman; BB, Tropical Composite; TC) to develop a novel framework termed correlation scan (CS). This framework was used to identify local regions associated with the genetic correlations between male and female fertility traits. Animals were genotyped with bovine high-density single nucleotide polymorphisms (SNPs) chip assay. The data used consisted of ~1000 individual records measured through frequent ovarian scanning for age at firstcorpus luteum(AGECL) and a laboratory assay for serum levels of insulin growth hormone (IGF1 measured in bulls, IGF1b, or cows, IGF1c). The methodology developed herein used correlations of 500-SNP effects in a 100-SNPs sliding window in each chromosome to identify local genomic regions that either drive or antagonize the genetic correlations between traits. We used Fisher’s Z-statistics through a permutation method to confirm which regions of the genome harboured significant correlations. About 30% of the total genomic regions were identified as driving and antagonizing genetic correlations between male and female fertility traits in the two populations. These regions confirmed the polygenic nature of the traits being studied and pointed to genes of interest. For BB, the most important chromosome in terms of local regions is often located on bovine chromosome (BTA) 14. However, the important regions are spread across few different BTA’s in TC. Quantitative trait loci (QTLs) and functional enrichment analysis revealed many significant windows co-localized with known QTLs related to milk production and fertility traits, especially puberty. In general, the enriched reproductive QTLs driving the genetic correlations between male and female fertility are the same for both cattle populations, while the antagonizing regions were population specific. Moreover, most of the antagonizing regions were mapped to chromosome X. These results suggest regions of chromosome X for further investigation into the trade-offs between male and female fertility. We compared the CS with two other recently proposed methods that map local genomic correlations. Some genomic regions were significant across methods. Yet, many significant regions identified with the CS were overlooked by other methods.

The goal of this study was to estimate genetic parameters and predict direct and correlated response to selection for lamb growth traits and ewe reproductive traits, based on single-trait selection or combining multiple traits in an optimum index that targets total litter post-weaning weight in the first lambing as the main selection goal. Heritability estimates ranged from 0.04 to 0.19. Genetic correlations between growth and reproductive traits ranged from −0.24 to 0.15. The indirect response to selection for reproductive traits in later lambings, by selecting on first lambing performance, was 11%–25% greater than direct selection. The response to indirect selection for composite reproductive traits, i.e., total weaning weight or total post-weaning weight, by selecting on individual lamb weaning weight or post-weaning weight was 1%–69% greater than direct selection, but it was accompanied by a negative response on litter size. However, combining alternate growth and reproductive traits in optimum selection index resulted in correlated response of up to 96% greater than direct selection response for reproductive traits without a negative response on litter size. Therefore, multiple trait selection using an index of component traits was more effective than direct selection for a composite trait.

The identification of functional genetic variants and associated candidate genes linked to feed efficiency may help improve selection for feed efficiency in dairy cattle, providing economic and environmental benefits for the dairy industry. This study used RNA-sequencing data obtained from liver tissue from 9 Holstein cows [n = 5 low residual feed intake (RFI), n = 4 high RFI] and 10 Jersey cows (n = 5 low RFI, n = 5 high RFI), which were selected from a single population of 200 animals. Using RNA-sequencing, 3 analyses were performed to identify: (1) variants within low or high RFI Holstein cattle; (2) variants within low or high RFI Jersey cattle; and (3) variants within low or high RFI groups, which are common across both Holstein and Jersey cattle breeds. From each analysis, all variants were filtered for moderate, modifier, or high functional effect, and co-localized quantitative trait loci (QTL) classes, enriched biological processes, and co-localized genes related to these variants, were identified. The overlapping of the resulting genes co-localized with functional SNP from each analysis in both breeds for low or high RFI groups were compared. For the first two analyses, the total number of candidate genes associated with moderate, modifier, or high functional effect variants fixed within low or high RFI groups were 2,810 and 3,390 for Holstein and Jersey breeds, respectively. The major QTL classes co-localized with these variants included milk and reproduction QTL for the Holstein breed, and milk, production, and reproduction QTL for the Jersey breed. For the third analysis, the common variants across both Holstein and Jersey breeds, uniquely fixed within low or high RFI groups were identified, revealing a total of 86,209 and 111,126 functional variants in low and high RFI groups, respectively. Across all 3 analyses for low and high RFI cattle, 12 and 31 co-localized genes were overlapping, respectively. Among the overlapping genes across breeds, 9 were commonly detected in both the low and high RFI groups (INSRR, CSK, DYNC1H1, GAB1, KAT2B, RXRA, SHC1, TRRAP, PIK3CB), which are known to play a key role in the regulation of biological processes that have high metabolic demand and are related to cell growth and regeneration, metabolism, and immune function. The genes identified and their associated functional variants may serve as candidate genetic markers and can be implemented into breeding programs to help improve the selection for feed efficiency in dairy cattle.

Summary Deviation from Mendelian inheritance expectations (transmission ratio distortion, TRD) has been observed in several species, including the mouse and humans. In this study, TRD was characterized in the turkey genome using both allelic (specific‐ and unspecific‐parent TRD) and genotypic (additive‐ and dominance‐TRD) parameterizations within a Bayesian framework. In this study, we evaluated TRD for 23 243 genotyped Turkeys across 56 393 autosomal SNPs. The analyses included 500 sires, 2013 dams and 11 047 offspring (trios). Three different haplotype sliding windows of 4, 10 and 20 SNPs were used across the autosomal chromosomes. Based on the genotypic parameterizations, 14 haplotypes showed additive and dominance TRD effects highlighting regions with a recessive TRD pattern. In contrast, the allelic model uncovered 12 haplotype alleles with the allelic TRD pattern which showed an underrepresentation of heterozygous offspring in addition to the absence of homozygous animals. For regions with the allelic pattern, only one particular region showed a parent‐specific TRD where the penetrance was high via the dam, but low via the sire. The gene set analysis uncovered several gene ontology functional terms, Reactome pathways and several Medical Subject Headings that showed significant enrichment of genes associated with TRD. Many of these gene ontology functional terms (e.g. mitotic spindle assembly checkpoint, DRM complex and Aneuploidy), Reactome pathways (e.g. Mismatch repair) and Medical Subject Headings (e.g. Adenosine monophosphate) are known to be related to fertility, embryo development and lethality. The results of this study revealed potential novel candidate lethal haplotypes, functional terms and pathways that may enhance breeding programs in Turkeys through reducing mortality and improving reproduction rate.

Genetic selection for carcass traits is paramount to maximize the profitability and long-term sustainability of any meat-producing livestock species. The main objectives of this research were to evaluate the efficiency of indicator traits for the genetic improvement of lamb carcass traits and to determine the value of including carcass traits into terminal sire selection indexes for the Canadian sheep industry. The carcass traits included hot carcass weight (HCW), fat depth at the GR site (FATGR) and average carcass conformation score (AVGCONF), and were measured on heavy lambs (slaughter age less than 365 days and HCW greater than 16.3 kg) in commercial abattoirs. Growth traits were found to be moderately efficient indicator traits for the genetic improvement of HCW but selection on ultrasound traits was necessary to substantially improve the carcass quality traits (FATGR and AVGCONF). Economic selection indexes were designed by adding various combinations of carcass traits into the Canadian Sheep Genetic Evaluation System terminal indexes. Records measured on individuals and progeny were assumed to be the sources of information for live animal and carcass traits, respectively. The changes in index accuracy, efficiency and expected correlated response were used to assess the value of their inclusion. HCW was found to have a large economic value, and its inclusion into terminal selection indexes was expected to substantially increase their accuracy (0.08-0.12 points) and efficiency (20%-30%). However, further including FATGR (measured 110 mm from the carcass midline over the 12th rib) and AVGCONF had little impact on the accuracy (≤0.03) and efficiency (1%-7%) of the proposed indexes. Thus, the inclusion of carcass traits into the existing terminal selection indexes could be beneficial for the genetic improvement of HCW, but further research is needed to determine optimal methods of increasing carcass fatness and muscularity.

Breeding stress-resilient livestock is a potential strategy to help mitigate the negative effect of environmental and pathogenic stressors. The hypothalamic-pituitary-adrenal axis and immune system are activated during stress events and release mediators into the circulation that help restore physiological homeostasis. The purpose of this study was to assess a comprehensive set of circulatory mediators released in response to an acute immune stress challenge to identify candidate biomarkers that can be used for the selection of stress-resilient animals. Fifteen female lambs were stress challenged with an intravenous bolus of lipopolysaccharide (LPS; 400 ng/kg), and blood was collected from the jugular vein at 0, 2, 4, and 6 h after LPS challenge to identify and monitor candidate stress biomarkers; temperature was also recorded over time. Biomarker responses were evaluated with a repeated-measures model to compare time points with baseline values. As expected, all sheep had a monophasic febrile response to LPS challenge, and cortisol increased and returned to baseline by 6 h. The cytokines tumor necrosis factor-α, IL-6, IFN-γ (proinflammatory), and IL-10 (anti-inflammatory) increased, but only tumor necrosis factor-α returned to baseline during the monitoring period. The cytokines IL-1α, IL-1β, IL-17α (proinflammatory), and IL-4 (anti-inflammatory) did not respond to LPS challenge. All chemokines (CCL2, CCL3, CCL4, CXCL10, and IL-8) responded to LPS challenge; however, only CCL2, CCL3, CCL4, and CXCL10 increased over time, and only CCL3, CCL4, and CXCL10 returned to baseline during the monitoring period. MicroRNA (miR-145, miR-233, and miR-1246) also increased and remained elevated during the study. In summary, the LPS challenge induced a strong stress response in Rideau-Dorset sheep that could be monitored with a distinct profile of circulatory biomarkers.

Regular changes in the environment and biological responses generate seasonal patterns in the reproduction in small ruminants. Breeding seasonality is a significant constraint impacting efficiency of lamb production. However, seasonality-related traits present a special peculiarity from a statistical point of view being circular data (day of year running 1:365). Recently, circular mixed models have been developed on the basis of the von Mises distribution and were applied to analyse lambing day distribution recorded from five major Canadian sheep breeds (Rideau Arcott, Romanov, Dorset, Suffolk and Polypay). In a simulation study, the linear model was not able to capture the variance components simulated under the circular paradigm; however, the von Mises model evidenced its ability to infer the variance components of simulated circular records. Using real data of sheep, mostly negligible variances were observed for additive genetic effect when using a linear model on circular data values. In contrast, when using the von Mises model, genetic variances were different across breeds, and it raises the possibility to delay the peak of reproduction and to change the seasonality of the ewes. However, a large variance was captured by flock-year effects emphasizing the strong influence of management in lambing seasons for Canadian sheep populations. Finally, the results suggest the potential of using the von Mises model to analyse circular data, and further research is needed for better understand the complexity of this trait and the von Mises models.

Made available in DSpace on 2022-05-01T15:46:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The aim of this study was to identify mRNA isoforms and small genetic variants that may be affecting marbling and beef color in Nellore cattle. Longissimus thoracis muscle samples from 20 bulls with different phenotypes (out of 80 bulls set) for marbling (moderate (n = 10) and low (n = 10) groups) and beef color (desirable (n = 10) and undesirable (n = 9) group) traits were used to perform transcriptomic analysis using RNA sequencing. Fourteen and 15 mRNA isoforms were detected as differentially expressed (DE) (P-value ≤ 0.001) between divergent groups for marbling and meat color traits, respectively. Some of those DE mRNA isoforms have shown sites of splicing modified by small structural variants as single nucleotide variant (SNV), insertion, and/or deletion. Enrichment analysis identified metabolic pathways, such as O2/CO2 exchange in erythrocytes, tyrosine biosynthesis, and phenylalanine degradation. The results obtained suggest potential key regulatory genes associated with these economically important traits for the beef industry and for the consumer. School of Agricultural and Veterinarian Sciences São Paulo State University (Unesp), SP National Council for Scientific and Technological Development (CNPq) College of Veterinary and Animal Science São Paulo State University (Unesp), SP Centre for Genetic Improvement of Livestock Department of Animal Biosciences University of Guelph School of Agricultural and Veterinarian Sciences São Paulo State University (Unesp), SP College of Veterinary and Animal Science São Paulo State University (Unesp), SP

Fecal egg count (FEC) is an indicative measurement for parasite infection in sheep. Different FEC methods may show inconsistent results. Not accounting for inconsistencies can be problematic when integrating measurements from different FEC methods for genetic evaluation. The objectives of this study were to evaluate the difference in means and variances between two fecal egg counting methods used in sheep—the Modified McMaster (LMMR) and the Triple Chamber McMaster (LTCM); to estimate variance components for the two FEC methods, treating them as two different traits; and to integrate FEC data from the two different methods and estimate genetic parameters for FEC and other gastrointestinal parasite resistance traits. Fecal samples were collected from a commercial Rideau-Arcott sheep farm in Ontario. Fecal egg counting was performed using both LMMR and the LTCM methods. Other parasite resistance trait records were collected from the same farm including eye score (FAMACHA), body condition score (BCS), and body weight (WT). The two FEC methods were highly genetically (0.94) and phenotypically (0.88) correlated. However, the mean and variance between the two FEC methods were significantly different (P < 0.0001). Therefore, re-scaling is required prior to integrating data from the different methods. For the multiple trait analysis, data from the two fecal egg counting methods were integrated (LFEC) by using records for the LMMR when available and replacing missing records with re-standardized LTCM records converted to the same mean and variance of LMMR. Heritability estimates were 0.12 ± 0.04, 0.07 ± 0.05, 0.17 ± 0.06, and 0.24 ± 0.07 for LFEC egg count, FAMACHA, BCS, and WT, respectively. The estimated genetic correlations between FEC and the other parasite resistance traits were low and not significant (P > 0.05) for FAMACHA (r = 0.24 ± 0.32) and WT (r = 0.22 ± 0.19), and essentially zero for BCS (r = −0.03 ± 0.25), suggesting little to no benefit of using such traits as indicators for LFEC.

Although the genetic correlation between complex traits have been estimated for more than a century, only recently we have started to map and understand the precise localization of the genomic region(s) that underpin these correlations. Reproductive traits are often genetically correlated, and yet we don9t fully understand the complexities, synergism, or trade-offs between male and female fertility. In this study, we used reproductive traits in two cattle populations to develop a novel framework termed correlation scan. This framework was used to identify regions associated with the genetic correlations between male and female fertility traits across the bovine genome. The traits used were age at first corpus luteum (AGECL) and serum levels of insulin growth hormone (IGF1 measured in bulls, IGF1b, or cows, IGF1c). The methodology developed herein used correlations of 500-SNP (single nucleotide polymorphism) effects in a 100-SNPs sliding window in each chromosome to identify regions in the genome that either drive (i.e., SNP effects on the same direction) or antagonize (i.e., SNP effects in the opposite direction) the genetic correlations between traits. We used a permutation test to confirm which regions of the genome harboured significant correlations. Hence, this framework can also identify neutral genomic regions with no effect on the pairwise trait studied. About 40% of the total genomic regions were identified as driving and antagonizing genetic correlations between male and female fertility traits in the two population. These regions confirmed the polygenic nature of the traits being studied and pointed to genes of interest. Quantitative trait loci (QTL) and functional enrichment analysis revealed that many significant windows co-located with known QTLs related to milk production and fertility traits, especially puberty. In general, the enriched reproductive QTLs driving the genetic correlations between male and female fertility are the same for both cattle populations, while the antagonizing regions were population specific. Moreover, most of the antagonizing regions were mapped to the chromosome X. These results suggest regions of the chromosome X for further investigation into the trade-offs between male and female fertility. Although the methodology was applied to cattle phenotypes, using high-density SNP genotypes, the general framework developed can be applied to any species or traits, and it can easily accommodate genome sequence data.

A variety of measures are currently used to evaluate feed efficiency in livestock, with some of the most popular being the linear regression of nutrient intake on the various energy sinks of the cohort being evaluated. The adoption of novel on-farm technologies has greatly increased the breadth and depth of data being collected on a daily basis, which creates the opportunity for the implementation of more advanced feed efficiency models. The objectives of the current study were to leverage data collected using high-throughput biometric technologies to evaluate changes of early-lactation feed efficiency on a daily basis and to develop a novel measure of feed efficiency based on the NRC net energy model. Daily records of nutrient intake, fat- and protein-corrected milk yield, body weight, and body condition score were used to model 7 different indices of feed efficiency (gross feed efficiency, return over feed costs, residual feed intake, residual net energy intake, and net energy efficiencies of lactation, maintenance, and body reserve flux) in primiparous Holstein heifers (n = 40) from 0 to 150 d in milk. We observed that feed efficiency was dynamic and fluctuated over the course of the experimental period regardless of the efficiency measure used, but most measures followed similar trends in changes of efficiency on a day-to-day basis. Of the measures evaluated, return over feed costs would be most suited for management purposes due to practicality and simplicity, whereas other measures, such as the efficiency of net energy flux to and from body reserves, present potential targets for inclusion in breeding goals. Net energy efficiency of lactation was estimated to have higher repeatability compared with residual feed or energy intake, which may reduce the time required to estimate whole-lactation efficiency. Because decreased net energy balance was strongly correlated with increased efficiency for all indices evaluated, future work investigating the associations of feed efficiency with the magnitude and duration of negative energy balance is warranted.

Realized deviations from the expected Mendelian inheritance of alleles from heterozygous parents have been previously reported in a broad range of organisms (i.e., transmission ratio distortion; TRD). Various biological mechanisms affecting gametes, embryos, fetuses, or even postnatal offspring can produce patterns of TRD. However, knowledge about its prevalence and potential causes in livestock species is still scarce. Specific Bayesian models have been recently developed for the analyses of TRD for biallelic loci, which accommodated a wide range of population structures, enabling TRD investigation in livestock populations. The parameterization of these models is flexible and allows the study of overall (parent-unspecific) TRD and sire- and dam-specific TRD. This research aimed at deriving Bayesian models for fitting TRD on the basis of haplotypes, testing the models for both haplotype- and SNP-based methods in simulated data and actual Holstein genotypes, and developing a specific software for TRD analyses. Results obtained on simulated data sets showed that the statistical power of the analysis increased with sample size of trios (n), proportion of heterozygous parents, and the magnitude of the TRD. On the other hand, the statistical power to detect TRD decreased with the number of alleles at each loci. Bayesian analyses showed a strong Pearson correlation coefficient (≥0.97) between simulated and estimated TRD that reached the significance level of Bayes factor ≥10 for both single-marker and haplotype analyses when n ≥ 25. Moreover, the accuracy in terms of the mean absolute error decreased with the increase of the sample size and increased with the number of alleles at each loci. Using real data (55,732 genotypes of Holstein trios), SNP- and haplotype-based distortions were detected with overall TRD, sire-TRD, or dam-TRD, showing different magnitudes of TRD and statistical relevance. Additionally, the haplotype-based method showed more ability to capture TRD compared with individual SNP. To discard possible random TRD in real data, an approximate empirical null distribution of TRD was developed. The program TRDscan v.1.0 was written in Fortran 2008 language and provides a powerful statistical tool to scan for TRD regions across the whole genome. This developed program is freely available at http://www.casellas.info/files/TRDscan.zip.

Heat stress negatively affects health and production in cows. Examining the cellular response to heat stress could reveal underlying protective molecular mechanisms associated with superior resilience and ultimately enable selection for more resilient cattle. This type of investigation is increasingly important as future predictions for the patterns of heat waves point to increases in frequency, severity, and duration. Cows identified as high immune responders based on High Immune Response technology (HIR) have lower disease occurrence compared to their average and low immune responder herd-mates. In this study, our goal was to identify epigenetic differences between high and low immune responder cows in response to heat stress. We examined genome-wide DNA methylation of blood mononuclear cells (BMCs) isolated from high and low cows, before and after in vitro heat stress. We identified differential methylation of promoter regions associated with a variety of biological processes including immune function, stress response, apoptosis, and cell signalling. The specific differentially methylated promoter regions differed between samples from high and low cows, and results revealed pathways associated with cellular protection during heat stress.

Understanding heat stress physiology and identifying reliable biomarkers are paramount for developing effective management and mitigation strategies. However, little is known about the molecular mechanisms underlying thermal tolerance in animals. In an experimental model of Sprague–Dawley rats subjected to temperatures of 22 ± 1°C (control group; CT) and 42°C for 30 min (H30), 60 min (H60), and 120 min (H120), RNA-sequencing (RNA-Seq) assays were performed for blood (CT and H120), liver (CT, H30, H60, and H120), and adrenal glands (CT, H30, H60, and H120). A total of 53, 1,310, and 1,501 differentially expressed genes (DEGs) were significantly identified in the blood (P < 0.05 and |fold change (FC)| >2), liver (P < 0.01, false discovery rate (FDR)–adjusted P = 0.05 and |FC| >2) and adrenal glands (P < 0.01, FDR-adjusted P = 0.05 and |FC| >2), respectively. Of these, four DEGs, namely Junb, P4ha1, Chordc1, and RT1-Bb, were shared among the three tissues in CT vs. H120 comparison. Functional enrichment analyses of the DEGs identified in the blood (CT vs. H120) revealed 12 biological processes (BPs) and 25 metabolic pathways significantly enriched (FDR = 0.05). In the liver, 133 BPs and three metabolic pathways were significantly detected by comparing CT vs. H30, H60, and H120. Furthermore, 237 BPs were significantly (FDR = 0.05) enriched in the adrenal glands, and no shared metabolic pathways were detected among the different heat-stressed groups of rats. Five and four expression patterns (P < 0.05) were uncovered by 73 and 91 shared DEGs in the liver and adrenal glands, respectively, over the different comparisons. Among these, 69 and 73 genes, respectively, were proposed as candidates for regulating heat stress response in rats. Finally, together with genome-wide association study (GWAS) results in cattle and phenome-wide association studies (PheWAS) analysis in humans, five genes (Slco1b2, Clu, Arntl, Fads1, and Npas2) were considered as being associated with heat stress response across mammal species. The datasets and findings of this study will contribute to a better understanding of heat stress response in mammals and to the development of effective approaches to mitigate heat stress response in livestock through breeding.

Crossbred beef steers, n = 5,140; 352 ± 5.45 kg initial body weight (BW) were used to evaluate chromium propionate supplementation to yearling steers in a commercial feedyard. Cattle were blocked by arrival date and initial BW and assigned randomly to pen within block; pens were randomly assigned to treatment within block. Treatments, replicated in 15 pens per treatment with 130 to 250 steers per pen, included: 1) control (CTL), 0 mg supplemental Cr/kg dietary dry matter (DM); 2) chromium (CR) 0.50 mg supplemental Cr/kg dietary DM (4.9 mg/d; chromium propionate; KemTRACE Chromium 0.4%, Kemin Industries, Des Moines, IA). Final BW, average daily gain (ADG) and gain efficiency (G:F) did not differ among treatments (P ≥ 0.26). Dry matter intake was greater for CR than CTL, 8.61 kg. vs. 8.49 kg, respectively (P = 0.03). Hot carcass weight (HCW), dressing percentage, ribeye area, and 12th-rib-fat were not different for CTL or CR (P ≥ 0.12). The percentage of carcasses camera grading choice or better was greater (P = 0.04) for CR (51.2%) than CTL (48%), and the percentage of select carcasses was less (P = 0.01) for CR (41.5%) than CTL (45.5%). Yield grade distribution did not differ among treatments (P ≥ 0.26). There was no difference (P ≥ 0.36) in overall morbidity (7.75%), or total mortality (1.43%) between treatments. Steers fed CR had higher quality carcasses, and similar G:F and HCW to CTL.

Parasitism by gastrointestinal nematodes (GINs) is a major source of morbidity and mortality for sheep flocks grazed on pasture. Since there is evidence for genetic resistance to GINs in some sheep breeds, genetic selection for immunologic resistance to GIN is a possible management strategy. This study sought to identify differences at the transcriptome level between Ridau-Arcott sheep characterized as high innate immune responders (IIRs, n=5) or high antibody-mediated immune responders (AbMIRs, n=5) following natural exposure to and infection with GINs after spending the summer on GIN-infested pasture; infection was confirmed with individual fecal egg counts. The transcriptomes of the high IIR and high AbMIR animals were also compared with GIN-naïve sheep of the same breed (all medium IIR and AbMIR responders, n = 7). Liver tissue samples from the 17 animals were used to perform transcriptomic analyses using RNA-Sequencing technology. The CLC Genomics Workbench 20.0.4 (CLC Bio, Aarhaus, Denmark) software was used to map reads to the most recent ovine reference genome (Oar rambouillet.v1.0.105), and for differential gene expression analysis. In total, 144 differentially expressed genes (DEG) were found between the high IIRs and the high AbMIRs (FDR< 0.05, and fold change (FC) abs > 2). When compared to the naïve animals, 136 and 53 DEG were found between them and the high IIRs and the high AbMIRs, respectively. In order to verify their function in the host immune response to GINs, functional enrichment analyses were performed on these candidate genes using the AmiGO2 software. Monocarboxilic acid metabolism was identified as an enriched biological process (FDR < 0.05), and ammonia-lyase activity and metalloendopeptidase activity were enriched molecular functions between the high IIR and high AbMIR animals (FDR < 0.05). These preliminary results improve understanding of how host resistance to GINs is genetically regulated through the innate and adaptive immune systems in sheep.

Pathogens induce neuroendocrine-immune interactions in their hosts, which are a basis to overcome the microbial stressor. These interactions result in individual variation of the hypothalamic-pituitary-adrenal (HPA) axis response and could contribute to variable stress resiliency. In present study, a comprehensive set of circulatory markers was assessed in variable stress responding lambs selected from a population (n = 112) and categorized based on cortisol levels as high (HSR, 336.2 ±27.9 nmol/L, n =12), middle (MSR, 147.3 ±9.5 nmol/L, n =12) and low (LSR, 32.1 ±10.4 nmol/L, n =12) responding phenotypes post LPS challenge (400 ng/kg iv). Blood was collected from the jugular vein at 0 (pre-) and 4 hrs post-LPS challenge to monitor changes in serum with a panel of 15 pro- and anti-inflammatory cytokines and chemokines and 84 miRNAs, and white blood cell (WBC) populations. The HSR had the strongest fever and pro-inflammatory IL-6, IFN-γ cytokine responses compared to MSR and LSR. HSR and MSR had stronger anti-inflammatory IL-10 cytokine and CCL2 chemokine responses than LSR. WBC counts changed between 0 and 4 hrs; however, no differences were detected among the variable stress response groups. Three miRNAs, oar-miR-485-5p (+3.82 folds), oar-miR-1193-5p (+2.43 folds) and oar-miR-3957-5p (+3.14 folds) were significantly (P < 0.05) upregulated, and seven miRNAs, oar-miR-376b-3p (-6.6 fold), oar-miR-376c-3p (3.5 folds), oar-miR-411b-5p (-11.69 folds), (oar-miR-376a-3p (-2.28 fold), oar-miR-376b-3p (-6.08 folds), oar-miR-376c-3p (-2.62 folds), oar-miR-381-3p (-3.85 folds) were downregulated (P < 0.05) in HSR compared to LSR and MSR. Functional analysis of miRNAs revealed their roles in activating TGF-beta signalling, Cytokine receptor interaction and Thyroid signalling pathways in HSR phenotypes indicating a hyper-induced acute-phase response. In summary, these results indicate variation in the acute-phase response to stress, and some of these markers could be used as stress biomarkers. Further investigation is warranted to understand the plausible association of cortisol phenotype with other important traits.

In the dairy industry, mate allocation is mainly based on the parents’ breeding values and inbreeding coefficients aiming to achieve the producer’s breeding goal. With artificial insemination, the portfolio of sires to choose from is large and the quality of the semen doses is standardized. However, not all sire-dam matings are equally likely to produce a successful pregnancy. Among other reproduction issues, the success of a mating could vary due to the incompatibility of gametes coming from the sire and the dam and could influence the fertilization’s success, additionally to the reproductive capacity of the parents. Considering the gametic incompatibility of the potential parents could be a novel option to improve mating plans. Under the hypothesis that gametic incompatibility has a significant effect on reproduction and reduces the odds of fertilization and pregnancy, this study aimed to determine the genetic background of gametic incompatibility. Transmission ratio distortion (TRD), which detects deviations from Mendelian inheritance expectations, is commonly used to identify deleterious mutations. We adapted the TRD model by including an interaction effect between the gametes leading to the offspring genotype to detect regions with TRD effects and gametic incompatibility. Our dataset contained 436,651 genotyped (50K SNP) Canadian Holstein cattle from 283,817 parents-offspring trios. A total of 482 regions with TRD containing 671 positional genes were found. The functional analysis detected biological pathways associated with uterus development, embryonic skeletal system development, and nervous system development. Additionally, gene ontology terms from the topology-based pathway enrichment analysis were mostly related to the steroid hormones signalling pathway. Although difficult, genes specific to gametic incompatibility could be differentiated from genes underlying other reproduction processes by refining the genetic regions with TRD. With further investigation, we will provide new information to improve mate allocation for the dairy cattle industry.

Reduced fertility is one of the main causes of economic losses in dairy farms. The cost of a stillbirth is estimated in US$ 938 per case in Holstein herds. Machine learning (ML) is gaining popularity in the livestock sector as a mean to identify hidden patterns and due to its potential to address dimensionality problems. Here we investigate the application of ML algorithms for the prediction of cows with higher stillbirth susceptibility in two scenarios: cows with >25% and >33.33% of stillbirths among birth records. These thresholds correspond to percentiles 75 (still_75) and 90 (still_90), respectively. A total of 10,570 cows and 50,541 birth records were collected to perform a haplotype-based genome-wide association study. Five-hundred significant pseudo single nucleotide polymorphisms (pseudo-SNPs) (False-Discovery Rate< 0.05) were used as input features of ML-based predictions to determine if the cow is in the top-75 and top-90 percentiles. Table 1 shows the classification performance of the investigated ML and linear models. The ML models outperformed linear models for both thresholds. In general, still_75 showed higher F1 values compared to still_90, suggesting a lower misclassification ratio when a less stringent threshold is used. We observe that accuracy of the models in our study is higher when compared to ML-based prediction accuracies in other breeds, e.g. compared to the accuracies of 0.46 and 0.67 that were achieved using SNPs for body weight in Brahman and fertility traits in Nellore, respectively. Xgboost algorithm shows the highest balanced accuracy (BA; 0.625), F1-score (0.588) and area under the curve (AUC; 0.688), suggesting that xgboost can achieve the highest predictive performance and the lowest difference in misclassification ratio between classes. The ML applied over haplotype libraries is an interesting approach for the detection of animals with higher susceptibility to stillbirths due to highest predictive accuracy and relatively lower misclassification ratio.

For the dairy industry, animal welfare and economic viability are key factors in determining the long-term sustainability of the industry. One challenge in lactating dairy cows is mastitis, as there are significant costs associated with each mastitis case due to treatment, milk loss, and potential cow culling. Differentially expressed (DE) genes, DE mRNA isoforms and DE long non-coding RNA (lncRNA) candidates were previously identified by our group between healthy and mastitic samples from six Holstein dairy cows. In total, 7 candidate genes, 5 mRNA isoforms and 4 lncRNA were targeted as they play an important role due to their association with mastitis or the immune system. The aim of the current research is to identify new structural variants in the transcriptome of these previously identified potential candidates using RNA-Sequencing. These structural variants could occur in both coding and intergenic regions of the genome and potentially impact the amino acid that is transcribed, creating a new functional or non-functional protein. In addition, whole genome sequencing (WGS) analysis was performed using hair samples collected from ten Holstein dairy cows (first lactation). Five of these animals had no previous reports of mastitis and five animals had at least one report of mastitis in her lifespan. The WGS results will be used to identify additional structural variants, especially within introns, of the previously identified candidates that could cause a genetic variation in individuals and an association to their susceptibility to mastitis disease.

Transmission ratio distortion (TRD) is a process when one allele from either parent is preferentially transmitted to the offspring. The identification of genomic regions affected by TRD might help in the detection of lethal alleles or potential genes affecting reproduction. Here, we investigated TRD in crossbreed beef cattle population aiming to identify genomic regions showing altered deviations in segregation that could be affecting reproduction performance. A total of 237 genotyped animals were used including 46 sires, 80 dams, and 111 parent-offspring (trios). The predominant breeds of these animals were Angus (61.83%), Simmental (18.99%), Gelbvieh (6.12%), Charolais (3.65%), Hereford (2.46%) and Limousin (1.57%). After excluding SNPs with minor allele frequency lower than 0.05 and call-rate lower than 0.90, a total of 369,902 autosomal SNPs were retained for further analyses. The SNP-by-SNP analysis was performed within a Bayesian framework using TRDscanv.2.0 software, using 100,000 iterations, with 10,000 iterations being discarded as burn-in. As table 1 shows, 33 SNPs were identified with TRD, considering a Bayes Factor (BF)≥100 and the approximate empirical null distribution of TRD at 0.01% margin error. Among them, 26 SNPs were parent-unspecific and 7 SNPs were parent-specific TRD. For parent-specific TRD, 214 were identified for sire- and 162 for dam-TRD (BF≥100). Among them, 4 SNPs were detected with sire- and dam-TRD in opposite direction of preference of transmission. Preliminary functional and positional analysis was performed using the list of TRD regions with BF≥100 and the approximate empirical null distribution of TRD at 0.01% margin error. For sire-TRD, 14% of the identified QTL (n = 254) were related to non-return rate. For dam-TRD, 21 regions related to conception rate were found (1.5%) and 13 regions related to stillbirth (0.93%). Haplotype analysis is in progress to identify additional candidate regions and alleles with TRD to better understand this phenomenon in a crossbreed beef population.

Genetically selecting animals that are heat tolerant can help to maintain production efficiency of the dairy industry under thermal challenges. During the summer months in Canada, dairy cows could be under thermal stress. For instance, in Ontario, cows are expected to be 105 days under thermal stress. The objective of this study was to estimate genetic parameters for milk production traits under heat stress in Canadian Holstein cows. A total of 604,050 test-day records for milk, fat, and protein yields from 78,516 first-lactation Holstein cows were used in this study. The production data was combined with daily maximum temperature-humidity index (THI; ranging from 30 to 83) calculated based on meteorological records from public weather stations. In total, 58 weather stations were located within a maximum distance of 20 km from each of the 1,284 herds included in this study. Single-trait random regressions on THI, fitting linear splines to describe the random additive genetic and permanent environmental effects, were used in the genetic analyses. Based on preliminary analyses, the knots of the spline functions were set to THI = 70, 57, and 58 for milk, fat, and protein yields, respectively. Therefore, the models assumed a linear effect of heat stress beyond the THI threshold, allowing to estimate the additive genetic effect under thermal comfort and at different levels of heat stress. The genetic correlations estimated between thermal comfort and heat stress were -0.09, -0.33, and -0.21 for milk, fat, and protein yields, respectively. This indicates an antagonistic relationship between level of production and heat tolerance. However, small differences in heritability estimates were observed above the THI thresholds (they ranged from 0.20 to 0.22 for milk, 0.18 to 0.15 for fat, and 0.14 to 0.15 for protein yields). This study demonstrates the possibility of genetically selecting for more heat-tolerant animals in Canada.

The aim of this study was to identify novel lncRNA differentially expressed (DE) between divergent animals for beef tenderness and marbling traits in Nellore cattle.

Ruminant supply chains contribute 5.7 gigatons of CO2-eq per annum, which represents approximately 80% of the livestock sector emissions. One of the largest sources of emission in the ruminant sector is methane (CH4), accounting for approximately 40% of the sectors total emissions. With climate change being a growing concern, emphasis is being put on reducing greenhouse gas emissions, including those from ruminant production. Various genetic and environmental factors influence cattle CH4 production, such as breed, genetic makeup, diet, management practices, and physiological status of the host. The influence of genetic variability on CH4 yield in ruminants indicates that genomic selection for reduced CH4 emissions is possible. Although the microbiology of CH4 production has been studied, further research is needed to identify key differences in the host and microbiome genomes and how they interact with one another. The advancement of “-omics” technologies, such as metabolomics and metagenomics, may provide valuable information in this regard. Improved understanding of genetic mechanisms associated with CH4 production and the interaction between the microbiome profile and host genetics will increase the rate of genetic progress for reduced CH4 emissions. Through a systems biology approach, various “-omics” technologies can be combined to unravel genomic regions and genetic markers associated with CH4 production, which can then be used in selective breeding programs. This comprehensive review discusses current challenges in applying genomic selection for reduced CH4 emissions, and the potential for “-omics” technologies, especially metabolomics and metagenomics, to minimize such challenges. The integration and evaluation of different levels of biological information using a systems biology approach is also discussed, which can assist in understanding the underlying genetic mechanisms and biology of CH4 production traits in ruminants and aid in reducing agriculture’s overall environmental footprint.

Genetic selection for improved feed efficiency in dairy cattle has received renewed attention over the last decade to address the needs of a growing global population. As milk yield is a critical component of feed efficiency metrics in dairy animals, our objective was to evaluate the associations between feed efficiency in primiparous Holstein cattle and parameters of a mathematical model describing individual lactation curves. The Dijkstra lactation curve model was fit to individual lactation records from 34 Holstein heifers with previously estimated measures of feed efficiency. We found that the optimal fit of the Dijkstra model was achieved using daily milk yield records up to 21 d in milk to capture the rise to peak milk yield and using monthly dairy herd improvement records for the remainder of lactation to accurately characterize lactation persistency. In the period of lactation before peak milk yield, improved feed efficiency was associated with a faster increase in daily milk yield over a shorter period of time at the expense of increased mobilization of body reserves; this serves to reinforce the concept that dairy cattle are primarily capital breeders versus income breeders. Feed efficiency in the period following peak lactation, as measured by gross feed efficiency, return over feed costs, and net energy efficiency of lactation, was positively associated with higher peak milk yield. The findings in early lactation suggest that estimates of feed efficiency could be improved by evaluating feed efficiency relative to conception, rather than parturition and lactation, to better account for the energy stored and released from body reserves in capital breeding.

Genome-wide association studies based on SNP have been completed for multiple traits in dairy cattle; however, copy number variants (CNV) could add genomic information that has yet to be harnessed. The objectives of this study were to identify CNV in genotyped Holstein animals and assess their association with hoof health traits using deregressed estimated breeding values as pseudophenotypes. A total of 23,256 CNV comprising 1,645 genomic regions were identified in 5,845 animals. Fourteen genomic regions harboring structural variations, including 9 deletions and 5 duplications, were associated with at least 1 of the studied hoof health traits. This group of traits included digital dermatitis, interdigital dermatitis, heel horn erosion, sole ulcer, white line lesion, sole hemorrhage, and interdigital hyperplasia; no regions were associated with toe ulcer. Twenty candidate genes overlapped with the regions associated with these traits including SCART1, NRXN2, KIF26A, GPHN, and OR7A17. In this study, an effect on infectious hoof lesions could be attributed to the PRAME (Preferentially Expressed Antigen in Melanoma) gene. Almost all genes detected in association with noninfectious hoof lesions could be linked to known metabolic disorders. The knowledge obtained considering information of associated CNV to the traits of interest in this study could improve the accuracy of estimated breeding values. This may further increase the genetic gain for these traits in the Canadian Holstein population, thus reducing the involuntary animal losses due to lameness.

Transmission ratio distortion (TRD) is defined as the observed deviation from the expected Mendelian inheritance of alleles from heterozygous parents. This phenomenon is attributed to various biological mechanisms acting on germ cells, embryos or fetuses, or even in early postnatal life. Current statistical approaches typically use two independent parametrizations assuming that TRD relies on allele- or genotype-related mechanisms, although they have never been tested and compared. This study compared allele- and genotype-related TRD models on simulated datasets with 1000 genotyped offspring and real data from 168 sire-dam-offspring beef cattle trios. The analysis of simulated datasets favored the true model of analysis in most cases (>93%), and a low percentage of missidentification occurred under (almost) null dominance (genotype-related model) or similar and moderate-to-low sire- and dam-specific TRD parameters (allele-related model). Moreover, the correlation between simulated and predicted distortion parameters was high (>0.97) under the true model. The comparison of allele- and genotype-related TRD models is an appealing tool to infer the biological source of TRD (i.e. haploid vs. diploid cells) when screening the whole genome. The analysis of beef cattle data corroborated a TRD region previously reported in chromosome 4, although discarding allele-related mechanisms and favoring the genotype-related model as the more reliable one. The results of this study highlight the relevance of implementing and comparing different parametrizations to capture all kinds of TRD, and to compare them using appropriate statistical methods.

BackgroundThe development of high-throughput sequencing and genotyping methodologies has enabled the identification of thousands of genomic regions associated with several complex traits. The integration of multiple sources of biological information is a crucial step required to better understand patterns regulating the development of these traits.FindingsGenomic Annotation in Livestock for positional candidate LOci (GALLO) is an R package developed for the accurate annotation of genes and quantitative trait loci (QTLs) located in regions identified in common genomic analyses performed in livestock, such as genome-wide association studies and transcriptomics using RNA sequencing. Moreover, GALLO allows the graphical visualization of gene and QTL annotation results, data comparison among different grouping factors (e.g., methods, breeds, tissues, statistical models, studies), and QTL enrichment in different livestock species such as cattle, pigs, sheep, and chickens.ConclusionsConsequently, GALLO is a useful package for annotation, identification of hidden patterns across datasets, and data mining previously reported associations, as well as the efficient examination of the genetic architecture of complex traits in livestock.

Improved reproductive efficiency could lead to economic benefits for the beef industry, once the intensive selection pressure has led to a decreased fertility. However, several factors limit our understanding of fertility traits, including genetic differences between populations and statistical limitations. In the present study, the RNA-sequencing data from uterine samples of high-fertile (HF) and sub-fertile (SF) animals was integrated using co-expression network meta-analysis, weighted gene correlation network analysis, identification of upstream regulators, variant calling, and network topology approaches. Using this pipeline, top hub-genes harboring fixed variants (HF &times, SF) were identified in differentially co-expressed gene modules (DcoExp). The functional prioritization analysis identified the genes with highest potential to be key-regulators of the DcoExp modules between HF and SF animals. Consequently, 32 functional candidate genes (10 upstream regulators and 22 top hub-genes of DcoExp modules) were identified. These genes were associated with the regulation of relevant biological processes for fertility, such as embryonic development, germ cell proliferation, and ovarian hormone regulation. Additionally, 100 candidate variants (single nucleotide polymorphisms (SNPs) and insertions and deletions (INDELs)) were identified within those genes. In the long-term, the results obtained here may help to reduce the frequency of subfertility in beef herds, reducing the associated economic losses caused by this condition.

The beef tenderization process during the post-mortem period is one of the most important sensorial attributes and it is well-established. The aim of this study was to identify the genetic contribution pattern to meat tenderness at 7-(LMD7), 14-(LMD14), and 21-(LMD21) days post-mortem. The heritabilities for LMD7 (0.194), LMD14 (0.142) and LMD21 (0.048) are well established in the population evaluated here. However, its genetic contribution in terms of genomic candidate regions is still poorly understood. Tenderness was measured in the Longissiums thoracis using Warner-Bratzler shear force in the three post-mortem periods. A total of 4323 crossbred beef cattle were phenotyped and genotyped using the Illumina BovineSNP50K. The percentage of the total genetic variance was estimated using the weighted single-step genomic best linear unbiased prediction method. The main candidate windows for LMD7 were associated with proteolysis of myofibrillar structures and the weakening endomysium and perimysium. Candidate windows for LMD14 and LMD21 were mapped in bovine QTLs for body composition, height and growth. Results presented herein highlight, the largest contribution of proteolysis related processes before 14-days post-mortem and body composition characteristics in later stages for meat tenderness.

Genetic parameters were estimated for growth, ultrasound, and carcass traits in a Canadian crossbred heavy lamb population. Traits analyzed included birth, weaning, post-weaning, and ultrasound scanning weights; pre- and post-weaning average daily gain; ultrasonically measured eye muscle and fat depths; hot carcass weight; fat depth at the GR site (110 mm from the midline on the 12th rib); carcass conformation scores; saleable meat yield; price grid value; and total carcass value. The impact of three alternative slaughter endpoints (slaughter age, carcass weight, and carcass fatness) on genetic parameter estimates was also evaluated. In general, carcass traits were found to be moderately heritable, with heritability estimates ranging from 0.17 ± 0.02 for hot carcass weight at a constant slaughter age to 0.34 ± 0.02 for average carcass conformation score at a constant carcass weight. Heritability estimates were similar when observations were adjusted to alternative slaughter endpoints, but for some traits, phenotypic variance and genetic correlation estimates differed. Genetic correlations between carcass traits and growth and ultrasound traits were typically favorable. Ultrasonically measured eye muscle depth and fat depth were found to be moderately to strongly positively correlated with hot carcass weight (0.33 ± 0.15 to 0.71 ± 0.19) and fat depth at the GR site (0.38 ± 0.14 to 0.74 ± 0.12), respectively, reaffirming the usefulness of selection on ultrasound traits to improve carcass yield and quality. Genetic correlations among carcass traits were generally favorable, with the exception of moderate unfavorable positive genetic correlations between fat depth at the GR site and primal cut carcass conformation scores (0.31 ± 0.05 to 0.60 ± 0.05). Overall, the results of this research suggest that there is potential to improve carcass yield and quality through genetic selection and provides the population-specific genetic parameter estimates needed for the genetic evaluation of carcass traits in the Canadian sheep population. Nevertheless, the optimal endpoint for carcass trait genetic evaluations will need to be further investigated, considering both the current findings and additional information on production practices in the industry.

Reduced fertility is one of the main causes of economic losses in dairy farms. The financial losses are estimated in US$938 per stillbirth case in Holstein herds. The identification of genomic regions associated with stillbirth could help to develop better management and breeding strategies aiming to reduce the frequency of undesirable gestation outcomes. The same cow may show different outcomes in different gestations. Therefore, evaluation of a single time-point may provide a biased indication of the genetic causes of stillbirth. A weighted single-step genomic best linear unbiased prediction (WssGBLUP) was performed using the BLUPF90 software. A total of 14,145 cows (with three or more delivery records) were genotyped for 42,909 SNP markers mapped against the ARS-UCD1.2 bovine reference genome. Three rounds of WssGBLUP were performed using 50,541 stillbirth records (4.8±1.3 records per animal). In total, 5,796 stillbirth cases were observed out of the 50,541 records (~11%). The statistical model included: calf size, calf sex, and dam age class (< 36, 36–50, 50–63, 63–75, ³75 months) as fixed effects; and herd-year-season, cow additive genetic merit, cow permanent environment, and service sire as random effects. Nine windows explaining more than one percent of the total genetic variance were identified, where the top 3 windows explained 7.86% (BTA13:37558814-38550118), 4.92% (BTA18:59897080-60892357) and 2.17% (BTA12:80568320-81508005). The top candidate window, on BTA13, harbors the OVOL2 gene, which codifies a zinc-finger protein crucial for embryo development during the angiogenesis, heart formation, hematopoietic, endothelial, neural tube and placental development. Additionally, OVOL2 is crucial during the spermatogenesis and was already identified as down-regulated between ectopic and eutopic endometrial tissues in woman with endometriosis. These results pinpoint new genomic candidate regions for stillbirth in Holstein, helping to better understand the genetic mechanisms associated with fertility problems.

The mRNA identification and associated splice variants affecting meat marbling in Nellore cattle could contribute to a better understanding of the genetic architecture of this complex trait. Longissimus thoracis samples from the 20 most extreme bulls (out of 80 bulls set) for marbling [high (n=10) and low (n=10) groups] trait were used to perform transcriptomic analysis using RNA-Sequencing. The CLC Genomics Workbench software was used to align the fragments of each sample to the bovine reference genome (ARS-UCD1.2) and to perform differential expressed transcript analysis (DE). An average of 37,000 transcripts and 14 mRNA DE (P ≤ 0.001; FC > 2) were detected in the muscle transcriptome. Among them, three transcripts were up-regulated (COL4A2-202, GHRH-201 and ENSBTAT00000070459.1) and 11 down-regulated (HBB-201, HBA-201, RPL14-202, CATHL1-201, CATHL4-201, MAPKAPK2-204, PCBD1-201, RPL30-203, NEURL1-202, PGLYRP1-201 and ENSBTAT00000038384.2) in high marbling group in relation to low group. Structural variants, including Single Nucleotide Variant (SNV), insertion or deletion were also found in the mRNA DE (4 in high and 6 in low marbling groups), causing possible splice site disruption. For high marbling group, in the COL4A2-202 transcript, three SNVs [one guanine (G) located on chromosome 12 at 85,104,867 bp, two cytosine (C), at the positions: 85,119,139 and 85,145,937 bp] were found. From these, one is a non-synonyms mutation [SNV (G) 85,145,937bp], causing an amino acid change (ENSBTAP00000005916.5: p.Glu1088Asp) in Collagen alpha-2(IV) chain protein (COL4A2). Interestingly, animals with low marbling presented also deletions (85,100,930 pb) in this same gene, causing an amino acid change (ENSBTAP00000005916.5:p.Pro113fs)in the COL4A2 protein. Functional enrichment analysis, using the DE mRNAs list, identified significant metabolic pathways (FDR < 0.05), such as O2/CO2 exchange in erythrocytes, tyrosine biosynthesis and phenylalanine degradation. The results suggest potential key regulatory genes associated with marbling, an economically important trait for the beef industry and for the consumer. Funding FAPESP (#2009/16118-5, #11/21241-0, #2017/02470-3, #2017/10630–2, #2018/ 20026–8, #2018/11154-2) and CAPES (#001).

Inorganic arsenic oxides have been identified as carcinogens in several human tissues, including epidermis. Due to the chemical similarity between trivalent inorganic arsenic (arsenite) and antimony (antimonite), we hypothesized that common intracellular targets lead to similarities in cellular responses. Indeed, transcriptional and proteomic profiling revealed remarkable similarities in differentially expressed genes and proteins resulting from exposure of cultured human epidermal keratinocytes to arsenite and antimonite in contrast to comparisons of arsenite with other metal compounds. These data were analyzed to predict upstream regulators and affected signaling pathways following arsenite and antimonite treatments. A majority of the top findings in each category were identical after treatment with either compound. Inspection of the predicted upstream regulators led to previously unsuspected roles for oncostatin M, corticosteroids and ephrins in mediating cellular response. The influence of these predicted mediators was then experimentally verified. Together with predictions of transcription factor effects more generally, the analysis has led to model signaling networks largely accounting for arsenite and antimonite action. The striking parallels between responses to arsenite and antimonite indicate the skin carcinogenic risk of exposure to antimonite merits close scrutiny.

Most current knowledge of sex determination in mammals has emerged from mouse and human studies. To investigate the molecular regulation of the sex determination process in cattle, we used an RNA sequencing strategy to analyze the transcriptome landscape of male and female bovine fetal gonads collected in vivo at key developmental stages: before, during, and after SRY gene activation on fetal days D35 (bipotential gonad formation), D39 (peak SRY expression), and D43 (early gonad differentiation). Differentially expressed genes (DEGs) were identified in male vs. female germinal ridges and among group genes showing similar expression profiles during the three periods. There were 143, 96, and 658 DEG between males and female fetuses at D35, D39, and D43, respectively. On D35, genes upregulated in females were enriched in translation, nuclear export, RNA localization, and mRNA splicing events, whereas those upregulated in males were enriched in cell proliferation regulation and male sex determination terms. In time-course experiments, 767 DEGs in males and 545 DEGs in females were identified between D35 vs. D39, and 3157 DEGs in males and 2008 in females were identified between D39 vs. D43. Results highlight unique aspects of sex determination in cattle, such as the expression of several Y chromosome genes (absent in mice and humans) before SRY expression and an abrupt increase in the nuclear expression of SOX10 (instead of SOX9 expression in the Sertoli cell cytoplasm as observed in mice) during male determination and early differentiation.

Selection based on scrapie genotypes could improve the genetic resistance for scrapie in sheep. However, in practice, few animals are genotyped. The objectives were to define numerical values of scrapie resistance genotypes and adjust for their non-additive genetic effect, evaluate prediction accuracy of ungenotyped animals using linear animal model, and predict and assess selection response based on estimated breeding values (EBV) of ungenotyped animals. The scrapie resistance (SR) was defined by ranking scrapie genotypes from low (0) to high (4) resistance based on genotype risk groups and was also adjusted for non-additive genetic effect of the haplotypes. Genotypes were simulated for 1,671,890 animals from pedigree. The simulated alleles were assigned to scrapie haplotypes in two scenarios of high (SRh) and low (SRl) resistance populations. A sample of 20,000 genotyped animals were used to predict ungenotyped using animal model. Prediction accuracies for ungenotyped animals for SRh and SRl were 0.60 and 0.54, and for allele content were from 0.41 to 0.71, respectively. Response to selection on SRh and SRl increased SR by 0.52 and 0.28, and on allele content from 0.13 to 0.50, respectively. In addition, the selected animals had large proportion of homozygous for the favorable haplotypes. Thus, pre-selection prior to genotyping could reduce genotyping costs for breeding programs. Using a linear animal model to predict SR makes better use of available information for the breeding programs.

The endangered cold-water fish species taimen (Hucho taimen) suffer acute temperature changes in culture and wild conditions. Understanding the effects of acute temperature changes on physiological processes of this species is essential for aquaculture practices and conservation. Liver transcriptomic profiles of the taimen (n = 24) exposed to acute temperature decrease (from 20 °C to 10 °C) and acute temperature increase (from 10 °C to 20 °C) was evaluated using high-throughput RNA-Sequencing. Samples were collected at day 0, 1, 7 and 35 in both treatments. Compared to day 0, the total numbers of differentially expressed genes (DEGs) in the taimen after acute temperature decrease were 173, 226 and 42 at day 1, 7 and 35, respectively, and the total numbers of DEGs following acute temperature increase were 260, 253 and 282 at day 1, 7 and 35, respectively. Particularly, 14 key regulatory genes were commonly found between both acute temperature treatments. Functional analysis based on the commonly identified DEGs revealed important metabolic pathways related to metabolism and immune function, suggesting a specific response mechanism of taimen against cold and heat shock. The results may assist in developing management strategies for stress mediation caused by acute temperature changes in the taimen and other cold water fish.

To understand genes, pathways, and networks related to puberty, we characterized the transcriptome of two tissues: the pituitary gland and ovaries. Samples were harvested from pre- and postpubertal Brahman heifers (same age group). Brahman heifers () are older at puberty compared with , a productivity issue. With RNA sequencing, we identified differentially expressed (DEx) genes and important transcription factors (TF) and predicted coexpression networks. The number of DEx genes detected in the pituitary gland was 284 ( < 0.05), and was the most DEx gene (fold change = 4.12, = 0.01). The gene promotes bone mineralization through transforming growth factor-β (TGFβ) signaling. Further studies of the link between bone mineralization and puberty could target . In ovaries, 3,871 genes were DEx ( < 0.05). Four highly DEx genes were noteworthy for their function: (a γ-aminobutyric acid [GABA] transporter), (), and () and its receptor . These genes had higher ovarian expression in postpubertal heifers. The GABA and its receptors and transporters were expressed in the ovaries of many mammals, suggesting a role for this pathway beyond the brain. The pathway has been known to influence the timing of puberty in rats, via modulation of GnRH. The effects of at the hypothalamus, pituitary gland, and ovaries have been documented. and its receptors are known factors in the release of GnRH, similar to and GABA, although their roles in ovarian tissue are less clear. Pathways previously related to puberty such as TGFβ signaling ( = 6.71 × 10), Wnt signaling ( = 4.1 × 10), and peroxisome proliferator-activated receptor (PPAR) signaling ( = 4.84 × 10) were enriched in our data set. Seven genes were identified as key TF in both tissues: , , , , , , and a novel gene. An ovarian subnetwork created with TF and significant ovarian DEx genes revealed five zinc fingers as regulators: , , , , and . Recent work of hypothalamic gene expression also pointed to zinc fingers as TF for bovine puberty. Although some zinc fingers may be ubiquitously expressed, the identification of DEx genes in common across tissues points to key regulators of puberty. The hypothalamus and pituitary gland had eight DEx genes in common. The hypothalamus and ovaries had 89 DEx genes in common. The pituitary gland and ovaries had 48 DEx genes in common. Our study confirmed the complexity of puberty and suggested further investigation on genes that code zinc fingers.

Puberty onset is a developmental process influenced by genetic determinants, environment, and nutrition. Mutations and regulatory gene networks constitute the molecular basis for the genetic determinants of puberty onset. The emerging knowledge of these genetic determinants presents opportunities for innovation in the breeding of early pubertal cattle. This paper presents new data on hypothalamic gene expression related to puberty in (Brahman) in age- and weight-matched heifers. Six postpubertal heifers were compared with 6 prepubertal heifers using whole-genome RNA sequencing methodology for quantification of global gene expression in the hypothalamus. Five transcription factors (TF) with potential regulatory roles in the hypothalamus were identified in this experiment: , , , , and . These TF genes were significantly differentially expressed in the hypothalamus of postpubertal versus prepubertal heifers and were also identified as significant according to the applied regulatory impact factor metric ( < 0.05). Two of these 5 TF, and , were zinc fingers, belonging to a gene family previously reported to have a central regulatory role in mammalian puberty. The gene belongs to the family of homologues of Drosophila sine oculis () genes implicated in transcriptional regulation of gonadotrope gene expression. Tumor-related genes such as and are known to affect basic cellular processes that are relevant in both cancer and developmental processes. Mutations in were associated with puberty in humans. Mutations in these TF, together with other genetic determinants previously discovered, could be used in genomic selection to predict the genetic merit of cattle (i.e., the likelihood of the offspring presenting earlier than average puberty for Brahman). Knowledge of key mutations involved in genetic traits is an advantage for genomic prediction because it can increase its accuracy.

In recent years, producers have combined the use of phenotypic appraisal and the estimation of breeding values (PTA or EPD) to make genetic selection decisions in beef and dairy cattle that have resulted in a steady genetic gain of 2% per year. However, the most extensive application of genomics has occurred in dairy with the estimation of molecular breeding values that has increased selection efficiency to a much higher order of magnitude. Despite a growing molecular and physiological understanding of complex traits, little is known about the genes determining the traits and their precise function, and a significant unexplained source of variation of phenotypes remains in livestock. Within this context, a more complete understanding of the genes and regulatory pathways and networks involved in economically important traits (i.e. feed efficiency and methane emissions, meat quality and carcass traits) in beef cattle will provide knowledge to help improve genetic selection and reproductive management. Therefore, high throughput -OMICS technology (i.e., transcriptomics, metagenomics, metabolomics, as well as epigenetics and gene networks amongst several others), will complement these tools and further advance identification of functional genes within a systems biology approach.

et al., Calorie restriction (CR) consistently extends longevity and delays age-related diseases across several animal models. We have previously shown that different dietary fat sources can modulate life span and mitochondrial ultrastructure, function and membrane fatty acid composition in mice maintained on a 40% CR. In particular, animals consuming lard as the main fat source (CR-Lard) lived longer than CR mice consuming diets with soybean oil (CR-Soy) or fish oil (CR-Fish) as the predominant lipid source. In the present work, a transcriptomic analysis in the liver and skeletal muscle was performed in order to elucidate possible mechanisms underlying the changes in energy metabolism and longevity induced by dietary fat in CR mice. After 8 months of CR, transcription downstream of several mediators of inflammation was inhibited in liver. In contrast, proinflammatory signaling was increased in the CR-Fish versus other CR groups. Dietary fish oil induced a gene expression pattern consistent with increased transcriptional regulation by several cytokines (TNF, GM-CSF, TGF-β) and sex hormones when compared to the other CR groups. The CR-Fish also had lower expression of genes involved in fatty acid biosynthesis and increased expression of mitochondrial and peroxisomal fatty acid β-oxidation genes than the other CR diet groups. Our data suggest that a diet high in n-3 PUFA, partially reverts CR-related changes in gene expression of key processes, such as inflammation and steroid hormone signaling, and this may mitigate life span extension with CR in mice consuming diets high in fish oil., This work was supported by NIH grant 1R01AG028125.

The Warner-Bratzler shear force (WBSF) and myofibrillar fragmentation index (MFI) are complementary methodologies used to measure beef tenderness. Longissimus thoracis samples from the 20 most extreme bulls (out of 80 bulls set) for WBSF (tender (n = 10) and tough (n = 10)) and MFI (high (n = 10) and low (n = 10)) traits were collected to perform transcriptomic analysis using RNA-Sequencing. All analysis were performed through CLC Genomics Workbench. A total of 39 and 27 transcripts for WBSF and MFI phenotypes were DE, respectively. The possible DE novel mRNA isoforms, for WBSF and MFI traits, are myosin encoders (e.g. MYL1 and MYL6). In addition, we identified potential mRNA isoforms related to genes affecting the speed fibers degradation during the meat aging process. The DE novel transcripts are transcripted by genes with biological functions related to oxidative process, energy production and striated muscle contraction. The results suggest that the identified mRNA isoforms could be used as potential candidate to select animals in order to improve meat tenderness.

The rapid development of DNA technologies, together with the adoption and daily routine use of commercial SNP arrays in livestock industries, provided a valuable resource of large and powerful data that can be explored for innovative applications for animal breeding purposes. Thus, the current availability of trios (i.e., sire-dam-offspring) of genotyped families enables the implementation of the transmission ratio distortion (TRD) approach to discover lethal alleles. Lethal alleles, which are crucial genetic determinants for reproduction, do not follow Mendelian principles but deviate from inheritance expectations, displaying signals of TRD. In this research, TRD was characterized using allelic (specific- and unspecific-parent TRD) and genotypic parameterizations (additive- and dominance-TRD) using both SNP- and haplotype-based methods. The analyses were performed using 258,140 Angus animals with 92,942 autosomal SNP genotypes, including 7,486 sires, 72,688 dams and 205,966 offspring. Across the whole genome, 852 regions displaying TRD were identified with different statistical significance. Among these findings, 19 haplotypes with recessive patterns (potential lethality for homozygote individuals) and 52 genomic regions with allelic patterns exhibiting complete or quasi-complete absence for homozygous individuals in addition to under-representation (potentially reduced viability) of heterozygous offspring were found. The average number of under-represented offspring (i.e., expected but not observed) across 52 allelic TRD regions ranged from 5,000 to 41,008. In contrast, the number of non-observed homozygous offspring for the 19 regions with recessive pattern ranges from 10 to 564. In addition, 64 and 20 genomic regions with TRD showed significant effects on the trait heifer pregnancy P < 0.05 and P < 0.01, respectively, reducing the progeny rate up to 15%. These novel findings in Angus present new candidate genomic regions putatively carrying lethal and semi-lethal alleles providing opportunities to reduce the rates of embryonic losses or death of offspring which could improve fertility and fitness in beef cattle populations.

Mastitis is a very costly and common disease in the dairy industry. The study of the transcriptome from healthy and mastitic milk somatic cell samples using RNA-Sequencing technology can provide measurements of transcript levels associated with the immune response to the infection. The objective of this study was to characterize the Holstein milk somatic cell transcriptome from 6 cows to determine host response to intramammary infections. RNA-Sequencing was performed on 2 samples from each cow from 2 separate quarters, one classified as healthy (n = 6) and one as mastitic (n = 6). In total, 449 genes were differentially expressed between the healthy and mastitic quarters (false discovery rate0.05, fold change±2). Among the differentially expressed genes, the most expressed genes based on reads per kilobase per million mapped reads (RPKM) in the healthy group were associated with milk components (CSN2 and CSN3), and in the mastitic group they were associated with immunity (B2M and CD74). In silico functional analysis was performed using the list of 449 differentially expressed genes, which identified 36 significantly enriched metabolic pathways (false discovery rate0.01), some of which were associated with the immune system, such as cytokine-cytokine interaction and cell adhesion molecules. Seven functional candidate genes were selected, based on the criteria of being highly differentially expressed between healthy and mastitic groups and significantly enriched in metabolic pathways that are relevant to the inflammatory process (GLYCAM1, B2M, CD74, BoLA-DRA, FCER1G, SDS, and NFKBIA). Last, we identified the differentially expressed genes that are located in quantitative trait locus regions previously known to be associated with mastitis, specifically clinical mastitis, somatic cell count, and somatic cell score. It was concluded that multiple genes within quantitative trait locus regions could potentially affect host response to mastitis-causing agents, making some cows more susceptible to intramammary infections. The identification of potential candidate genes with functional, statistical, biological, and positional relevance associated with host defense to infection will contribute to a better understanding of the underlying genetic architecture associated with mastitis. This in turn will improve the sustainability of agricultural practices by facilitating the selection of cows with improved host defense leading to increased resistance to mastitis.

Detecting combinations of alleles that diverged between subpopulations via selection signature statistics can contribute to decipher the phenomenon of epistasis. This research focused on the simulation of genomic data from subpopulations under divergent epistatic selection (ES). We used D’IS2 and FST statistics in pairs of loci to scan the whole-genome. The results showed the ability to identify loci under additive-by-additive ES (ESaa) by reporting large statistical departures between subpopulations with a high level of divergence, while it did not show the same advantage in the other types of ES. Despite this, limitations such as the difficulty to distinguish between the quasi-complete fixation of one locus by ESaa from other events were observed. However, D’IS2 can detect loci under ESaa by defining a minimum boundary for the minor allele frequency on a multiple subpopulation analysis where ES only takes place in one subset. Even so, the major limitation was distinguishing between ES and single-locus selection (SS); therefore, we can conclude that divergent locus can be also a result of ES. The test conditions with D-statistics of both Ohta (1982a, 1982b) and Black and Krafsur (1985) did not provide evidence to differentiate ES in our simulation framework of isolated subpopulations.

Background Ketosis in dairy cattle has been shown to cause a high morbidity in the farm and substantial financial losses to dairy farmers. Ketosis symptoms, however, are difficult to identify, therefore, the amount of ketone bodies (mainly β-hydroxybutyric acid, BHB) is used as an indicator of subclinical ketosis in cows. It has also been shown that milk BHB concentrations have a strong correlation with ketosis in dairy cattle. Mid-infrared spectroscopy (MIR) has recently became a fast, cheap and high-throughput method for analyzing milk components. The aim of this study was to perform a genome-wide association study (GWAS) on the MIR-predicted milk BHB to identify genomic regions, genes and pathways potentially affecting subclinical ketosis in North American Holstein dairy cattle. Results Several significant regions were identified associated with MIR-predicted milk BHB concentrations (indicator of subclinical ketosis) in the first lactation (SCK1) and second and later lactations (SCK2) in Holstein dairy cows. The strongest association was located on BTA6 for SCK1 and BTA14 on SCK2. Several SNPs on BTA6 were identified in regions and variants reported previously to be associated with susceptibility to ketosis and clinical mastitis in Jersey and Holstein dairy cattle, respectively. One highly significant SNP on BTA14 was found within the DGAT1 gene with known functions on fat metabolism and inflammatory response in dairy cattle. A region on BTA6 and three SNPs on BTA20 were found to overlap between SCK1 and SCK2. However, a novel region on BTA20 (55–63 Mb) for SCK2 was also identified, which was not reported in previous association studies. Enrichment analysis of the list of candidate genes within the identified regions for MIR-predicted milk BHB concentrations yielded molecular functions and biological processes that may be involved in the inflammatory response and lipid metabolism in dairy cattle. Conclusions The results of this study confirmed several SNPs and genes identified in previous studies as associated with ketosis susceptibility and immune response, and also found a novel region that can be used for further analysis to identify causal variations and key regulatory genes that affect clinical/ subclinical ketosis. Electronic supplementary material The online version of this article (10.1186/s12863-019-0761-9) contains supplementary material, which is available to authorized users.